肥胖发生与白色脂肪过度分化和棕色脂肪缺乏密切相关。I型11β羟基类固醇脱氢酶（11β-HSD1）通过活化糖皮质激素参与白色脂肪细胞分化，但该酶在棕色脂肪细胞分化，特别是白色脂肪组织棕色化过程中的分子机制鲜有报道。在前国自然资助下发现，在高脂饮食诱导的肥胖小鼠中抑制该酶在白色脂肪组织内的表达，可以显著降低体脂含量，并诱导白色脂肪组织特异性表达UCP1等基因，使白色脂肪呈现棕色脂肪特征。据此提出假说：11β-HSD1通过活化糖皮质激素调控脂肪细胞分化方向，抑制该酶使白色脂肪分化受阻，启动β3-AR-cAMP-PKA棕色化信号通路，增加耗能，缓解肥胖。本课题拟利用小鼠和细胞模型，应用过表达和RNA 干扰等技术手段，从分子、细胞、动物等多层次明确该酶在脂肪细胞分化中的作用，阐明其作为干预靶点在白色脂肪棕色化过程中的作用机制。本课题将从白色脂肪棕色化新视角探讨肥胖的发生机制，为肥胖防治提供新思路。

The occurrence of obesity is closely related to excessive differentiation of white adipose tissue and the lack of brown adipose tissue. Recently 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) was discovered stimulating white adipocytes differentiation through activation of glucocorticoids, while rare reports discussed this enzyme in the brown adipocytes differentiation, especially molecular mechanism in the process of white adipocytes swithching into brown adipocytes. With the former National Natural Science Foundation of China(No. 81270948), inhibition of the enzyme in white adipose tissue of high-fat diet induced obesity mice could significantly reduce body fat mass and promote the expression of UCP1 gene, so that the white adipose tissue resembled characteristics of brown adipose tissue. Thus we hypothesize that 11β-HSD1 through activation of glucocorticoid regulates direction of adipocytes differentiation, inhibition of the enzyme attenuates white adipocytes differentiation, and initiates β3-AR-cAMP-PKA browing signalling pathway, increases energy expenditure, reduces obesity. To verify this hypothesis, we will use mice and cell models through adenovirus overexpression and RNA interference technical methods, from molecular, cellular and the overall multi-level to explore the role of this enzyme in adipocyte differentiation, clarify its molecular mechanism as a intervention target in the process of adipocytes browning. We will provide novel insight into obesit from white adipocytes browning, and provide new way for preventing obesity.